DNA base flipping is defined as the ability of a base to flip out of double helix in an extrahelical configuration.[1] This mechanism was first observed in 1994 by X-ray crystallography for the C5-cytosine DNA methyltransferase from Haemophilus Haemolyticus (M. Hhal)by Klimasauskas and colleagues.[2] When the 2.8Å structure was observed, authors described that the cytosine residue was able to swing completely out of the double helix and it was positioned in the active site of the Hhal methyltransferase, which in turn, caused a major conformational change on the enzyme. These observations lead to the hypothesis of this feature be employed by other proteins like helicases, recombination enzymes, RNA polymerases, DNA polymerases, and Type II topoisomerases.[3]
^University, James D. Watson, Cold Spring Harbor Laboratory, Tania A. Baker, Massachusetts Institute of Technology, Alexander Gann, Cold Spring Harbor Laboratory, Michael Levine, University of California, Berkeley, Richard Losik, Harvard (2014). Molecular biology of the gene (Seventh edition ed.). Boston: Pearson/CSH Press., ISBN978-0-321-76243-6.